Long non-coding antisense RNA GAS6-AS1 supports gastric cancer progression via increasing GAS6 expression.

OBJECTIVE:As one broader class of non-coding RNAs (lncRNAs), non-coding antisense (AS) transcripts are functionally characterized to play pivotal roles in various pathophysiological processes, including tumor biology. METHODS:In this study, the exact biological functions and regulation mechanisms of GAS6-AS1 in gastric cancer (GC) was examined. RESULTS:The expression of GAS6-AS1 was markedly upregulated in GC tissues and is associated with advanced stage (III + IV) of GC patients. Gain-of-function and loss-of-function experiments showed that GAS6-AS1 promoted cell proliferation, migration, invasion ability in vitro and xenograft tumor growth in vivo by promoting entry into S-phase. The mechanistic investigations showed that GAS6-AS1 can control the expression of its cognate sense gene GAS6 at the transcriptional or translational levels by forming a RNA-RNA duplex, consequently inducing an increase of AXL level and driveling AXL signaling pathway activation. CONCLUSIONS:Taken together, our studies indicate that GAS6-AS1 significantly driving the aggressive phenotype in GC through activating its cognate sense gene GAS6, and provides a more complete understanding of GAS6-AS1 as a potential therapeutic target for GC.

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